Low back pain poses a significant socioeconomic burden with a lifetime prevalence of 84% and estimated U.S. expenditures of $85.9 billion per year. Although the cause of low back pain is difficult to pinpoint; it often originates from degenerating or herniated intervertebral discs. As shown in FIG. 1, an intervertebral disc 12 includes the nucleus pulposus 10 surrounded by the annulus fibrosus 16. A disc 12 forms a cushion between adjacent vertebrae 14 that allows for flexibility and motion and supports compressive loads during activities of daily living. The nucleus pulposus is a highly hydrated tissue composed primarily of type II collagen and the proteoglycan aggrecan. Intervertebral disc degeneration is a multifactorial process that manifests initially as biochemical degradation of the nucleus pulposus 10. Intervertebral disc herniation is commonly the result of an increase in intradiscal pressure due to abrupt loading that exceeds the strength of the restraining annulus fibrosus 16 of the disc 12 leading to extrusion of nucleus pulposus tissue 10 from the disc 12. Both pathologies can result in decreased disc height and irritation of adjacent nerve roots leading to the generation of back and leg pain as well as limb weakness.
Current therapies for both intervertebral disc degeneration and herniation are palliative and merely delay invasive surgical management in the form of discectomy, spinal fusion and total disc replacement. While these procedures may temporarily relieve pain, they do not attempt to replace, restore or regenerate healthy nucleus pulposus tissue. Additionally, there are concerns with the use of surgical methodologies that may promote re-herniation, altered spinal biomechanics, and accelerated degeneration in adjacent discs.
Regenerative medicine approaches to intervertebral disc degeneration repair have been investigated both in vitro and in vivo. For instance, injection of growth factors and stem cells into the nucleus pulposus have been examined, but have demonstrated limited success due short half-life, leakage, and inability to maintain an appropriate phenotype due to the altered tissue extracellular matrix (ECM) microarchitecture.
Tissue engineering strategies combining a supporting scaffold and an alternative healthy cell source (i.e. stem cells) together provide a promising avenue for developing viable nucleus pulposus tissue constructs. However, success of such approaches relies largely upon the development of a biomaterial scaffold that mimics the biochemistry and mechanical properties of the subject and that can function to deliver, protect, and provide instructive cues to stem cells such that they attain the appropriate phenotype and produce nucleus pulposus-specific ECM. Examples of biomaterial scaffolds investigated include pre-formed and injectable hydrogels composed of type II collagen-hyaluronic acid and cross-linked alginate.
An alternative scaffold formation method includes the decellularization of a source tissue. Decellularization attempts to remove host cells from the source tissue while maintaining intact, tissue-specific ECM. One primary advantage of this approach is that the remaining ECM provides cues that can advantageously affect migration, proliferation, differentiation and subsequent tissue-specific ECM production by seeded cells. Successful decellularization has proven difficult however, as it requires complete removal of potential immunogenic materials while maintaining suitable levels of desirable ECM components such that function of the scaffold can be maintained. Attempts have been made to form suitable implantable graft materials from xenograft or allograft sources. While some approaches have demonstrated the ability to retain key ECM components in physiologically relevant quantities and ratios, these methods unfortunately left the source cells devitalized but sequestered within the tissue. Others have demonstrated successful removal of cell DNA via disruption of the native ECM, but the resulting scaffold material also showed significant reduction in GAG, which would significantly affect function of the resulting graft material.
What is needed in the art is a biomaterial scaffold that can recapitulate native nucleus pulposus microarchitecture, biochemistry, and mechanical properties, and that can support cells seeded thereon as a route to aiding patients with intervertebral disc degeneration and intervertebral disc herniation.